The goal of this project is to develop a technology for site-specific tritiation of oligonucleotides to a high specific activity (larger than equeal to 30 Ci/mmol). Synthetic oligonucleotides are potentially powerful drugs that can target specific DNA and RNA sequences associated with various diseases. Successful development of oligonucleotides into acceptable pharmaceuticals requires extensive pharmacokinetic and pharmacodynamic studies which are currently limited by the lack of oligonucleotides radiolabeled at specific sites to a high specific activity. The applicants propose here an innovative strategy for making tritiated oligonucleotides from precursors containing a halogenated base in a specific site. The halogenated oligonucleotides can be synthesized with commercially available halogenated phosphoroamidites of different deozynucleosides. The exchange of tritium for halogen is achieved via a tritiation process that they have developed into commercial applications. They propose to remove unreacted halogenated oligonucleoties with antibodies against halogenated monomers. Successful substitution of tritium for halogen in precursors will generate 3H-oligonucleotides with a specific activity of approximately 30 Ci/mmole (one tritium atom per molecule). To obtain higher specific activities several halogenated monomers may be introduced in a precursor oligonucleotide. PROPOSED COMMERCIAL APPLICATION: The results of this project would allow them to offer a commercial service of site-specific tritiation of conventional and modified oligonucleotides to industrial and academic laboratories.